1. Field of the Invention
The present invention relates to an antibody or a monoclonal antibody for quantitative determination of hepatocyte growth factor activator inhibitor-1 (hereinafter, sometimes abbreviated as “HAI-1”), to a method of using the same and to a kit for measuring the same. Also, the present invention relates to a method of detecting and measuring the state of a patient suffering from a disease, In particular inflammation of an organ, nephritis, cancers, liver diseases, blood diseases, myocardial infarction, angina pectoris, cerebral infarction, or thrombosis.
2. Description of the Related Art
The hepatocyte growth factor activator inhibitor-1 (HAI-1) is known as a control agent for a hepatocyte growth factor inhibitor and as a kind of Kuniz type serine protease inhibitor (Shimomura et al., J. Biol. Chem., 272: 6370–6376 (1997)). HAI-1 is considered to be a protein that has a portion that penetrates through a cytoplasmic membrane (hereinafter, referred to as “cytoplasmic membrane-penetrating portion”) and is reported to have a molecular weight of about 66,000 (electrophoresis) (Shimomura et al., J. Biol. Chem., 126: 821–828 (1999)). Also, HAI-1 is known to exist in the supernatant of a culture of HAI-1-producing culture cells, such as MKN45, in a state where it has no cytoplasmic membrane-penetrating portion. It has been reported through the measurement by using an SDS-PAGE method under the reduction condition that these soluble HAI-1 molecules include a molecule having a molecular weight of about 58,000, a molecule having a molecular weight of about 48,000, a molecule having a molecular weight of about 40,000, and a molecule having a molecular weight of about 39,000, which are called “soluble forms of HAI” (Shimomura et al., J. Biol. Chem., 126: 821–828 (1999)); herein these are referred to as “soluble HAI-1.”
It has been known that HAI-1 has the effect of a protease inhibitor such as the effect of inhibiting a hepatocyte growth factor-activating factor [which is a factor that acts on a hepatocyte growth factor (hereinafter, abbreviated as “HGF” (Naka et al., J. Biochem., 267: 20114–20119 (1992)) and subjecting it to specific restricted decomposition to activate it (Shimomura et al., Cytotechnology, 8:219–229 (1992))]. The known antibody to HAI-1 includes murine monoclonal antibodies C76-18 and 1N7 (Shimomura et al., JP 11-295309 A: C76-18, Kataoka et al., J. Histochem. Cytochem., 47: 673–682 (1999): 1N7). Tissue staining using this antibody has revealed that HAI-1 is expressed in pancreas, liver, small intestine and uterus of normal persons. Tissue staining using the above-mentioned antibody has been performed for patients suffering from liver cancer and expression of HAI-1 has been examined (Kataoka et al., Cancer Research, 60, 6148–6159, 2000). However, the role and function of HAI-1 in human pathology have not been clarified yet. Further, the relationship between the concentration of soluble HAI-1 in the biological components such as blood and the pathology has not been known.
To analyze the relationship between the concentration of soluble HAI-1 in the biological components, such as blood level, and the pathology, it is necessary to quantitatively determine soluble HAI-1 that exists in the biological components such as human tissue, body fluid, urine or blood. Then, to quantitatively determine soluble HAI-1, it is indispensable to obtain a high-affinity antibody that recognizes soluble HAI-1, particularly desirably a high-affinity monoclonal antibody.
The known antibody to HAI-1 includes murine monoclonal antibodies C76-18 and 1N7 (Shimomura et al., JP 11-295309 A: C76-18, Kataoka et al., J. Histochem. Cytochem., 47: 673–682 (1999): 1N7). However, there has been no anti-soluble HAI-1 antibody having suitable properties for quantitatively determining soluble HAI-1 or no method or kit therefor for detecting or quantitatively determining soluble HAI-1 existing in the biological components such as human blood.